The Mouse Management Component supports 2 full-time animal technician position equivalents (in practice, approximately one half-time position for each project). These individuals are fully trained and engaged in the maintenance of gene-targeted and transgenic mouse models, as proposed in the individual projects. This component has the necessary equipment and space in a pathogen-free mouse-specific vivarium, as detailed below. The actual production of new mouse models will be done through the currently established UCSD Transgenic Mouse and Embryonic Stem Cell Gene Targeting Core (for details, please see the web site http://cancer.ucsd.edu/Research/Shared/tgm/default2.asp). This state-of-the-art facility has an excellent track record in the production of genetically altered mice. Thus, rather than doing gene targeting ourselves, it makes sense for the PEG to pay this established UCSD Core a fee-for-service for the generation of mice. While the total costs are about the same, we do avoid duplicative functions at the institution. Our past experience with this approach has been good. We will of course also take advantage of the ongoing targeting projects at the Knockout Mouse Project (KOMP) (http://www.komp.org/) Based on our experience to date in similar projects, we also feel it is best to keep the daily management and breeding of mice, the animal technicians involved, the costs of mouse cage space, and the use of approaches such as Speed Congenics as Core functionsrather than allocating resources to each project for these activities. This approach also reduces waste and allows the maximum flexibility in accommodating the needs of all the projects, which will vary from year to year While this makes for a rather large budget for an Administrative Core, most of the budget is actually for mouse-related costs relevant to all projects. Almost all of the specific aims of all of the projects and the functions of the other Cores require the use of mice, which will be managed by Core C. Likewise, the administrative component is important for all Projects and Cores. Thus. Core C will effectively support all of the other Projects and Cores.